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Cortisol Regulation in Polycystic Ovary Syndrome (PCOS)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by Oregon Health and Science University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT00694759
First received: June 6, 2008
Last updated: August 3, 2010
Last verified: August 2010
  Purpose

The purpose of this study is to determine if insulin resistance (how well the body uses insulin and clears sugar) can affect cortisol levels in normal healthy women and women with polycystic ovary syndrome of all body weights.


Condition Intervention
Polycystic Ovary Syndrome
Drug: pioglitazone
Drug: metformin
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Cortisol Regulation in Polycystic Ovary Syndrome

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • The comparison of body surface area adjusted cortisol production rate (CPR/BSA) before and after insulin sensitizing therapy in women with PCOS. [ Time Frame: Before and after 6 months of insulin sensitizing therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparisons of 24-hour values for adrenocorticotropic hormone , free-cortisol, and cortisol binding globulin. [ Time Frame: Before and after 6 months of insulin sensitizing therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 107
Study Start Date: October 2006
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Pioglitazone will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.
Drug: pioglitazone
30 mg for 2 weeks, then 45 mg daily
Other Name: Actos
Active Comparator: B
Metformin will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.
Drug: metformin
500mg twice daily for 1 week, then 1000 mg twice daily
Other Names:
  • Glucophage
  • Glucophage XR
Placebo Comparator: C
Placebo will be given to women with PCOS. After one month and six months of therapy, measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.
Drug: placebo
capsule twice daily

Detailed Description:

PCOS is a common clinical problem affecting young women, characterized by oligomenorrhea and hyperandrogenism. Central obesity and insulin resistance are also prominent features of PCOS, and in addition are important risk factors for development of hypertension, hyperlipidemia and atherosclerotic heart disease. Previous studies have suggested that cortisol is dysregulated in PCOS, primarily through increased hypothalamic-pituitary-adrenal (HPA) axis activity and enhanced cortisol secretion. Increased adrenocorticotropic hormone (ACTH) secretion could also potentially lead to elevated adrenal androgen production in PCOS. Techniques used in previous studies have been inconsistent, however, and a link between increased HPA axis activity and the phenotypic changes in PCOS has not been clearly demonstrated. Cortisol is also produced from cortisone in peripheral adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (HSD 1), suggesting another potential point of dysregulation that may contribute to central obesity and insulin resistance in PCOS. Further investigation of both central and peripheral regulation of cortisol is necessary to better understand the pathophysiology of PCOS.

Specific Aim 1: To perform a cross-sectional study of women with PCOS and normal controls matched for age and body mass index, and measure insulin sensitivity and visceral fat, as well as (a) 24-hour CPR, ACTH, free cortisol, and cortisol binding globulin (CBG), (b) adipocyte, liver, and whole body HSD 1 activity, and (c) androgen levels.

Specific Aim 2: To prospectively administer pioglitazone or metformin to women with PCOS in a placebo-controlled trial, and after one month and six months of therapy measure (a) 24-hour CPR, ACTH, free cortisol, and CBG, (b) adipocyte, liver, and whole body HSD 1 activity, and (c) insulin sensitivity, visceral fat, and androgen levels.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (Healthy controls):

  • Healthy
  • At lifetime maximal weight
  • Weight stable for at least 6 months prior to study entry
  • Willing to commit to not making significant changes to their diet or daily activities while enrolled.
  • Premenopausal
  • Have regular menstrual cycles
  • No evidence of hirsutism

Additional Inclusion Criteria (Subjects with PCOS):

  • Clinical findings of amenorrhea or oligomenorrhea dating from menarche
  • Clinical and/or biochemical evidence of hyperandrogenism
  • Exclusion of related disorders

Exclusion Criteria (Healthy controls):

  • Less than 18 years of age
  • Exercise > 30 minutes/day, 3 times a week
  • Smokers
  • Heavy alcohol drinkers (> 2 drinks/day)
  • Type 2 diabetes
  • Medical diagnoses including heart disease and cancer
  • Psychiatric illness (i.e.depression, psychosis, bipolar, schizophrenia)
  • Body weight > 136 kg
  • Pregnant
  • Endocrine diseases affecting body composition or androgen levels

Additional Exclusion Criteria (Subjects with PCOS):

  • Laboratory evidence of hyperprolactinemia, thyroid dysfunction, or 21-hydroxylase-deficient nonclassic CAH
  • Contraindication to pioglitazone (i.e. CHF, impaired liver function, anemia, depressed leukocyte counts, pulmonary disease, known sensitivity to thiazolidinediones.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694759

Contacts
Contact: Bethany J Klopfenstein, MD 503-494-4020 klopfens@ohsu.edu
Contact: Jonathan Q Purnell 503-494-1056 purnellj@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Bethany J. Klopfenstein, MD         
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Bethany J. Klopfenstein, MD Oregon Health and Science University
  More Information

No publications provided

Responsible Party: Bethany Klopfenstein, MD, Oregon Health & Science University
ClinicalTrials.gov Identifier: NCT00694759     History of Changes
Other Study ID Numbers: OHSUIRB00002532
Study First Received: June 6, 2008
Last Updated: August 3, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
Polycystic ovary syndrome
insulin
PCOS
cortisol regulation
regulation

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Syndrome
Adnexal Diseases
Cysts
Disease
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Pathologic Processes
Cortisol succinate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Metformin
Pioglitazone
Anti-Inflammatory Agents
Dermatologic Agents
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014